Thyroid hormone synthesis depends on a complex series of steps. These include transport of iodide, iodination and storage of thyroglobulin, and the processing of thyroglobulin with release of thyroid hormones. Earlier studies in this laboratory concentrated on the first step in thyroid hormone synthesis by characterizing iodide transport and the regulation of this process by TSH and adrenergic agents. Studies over the last several years have concentrated on the events subsequent to this transport. One study involves familial goiter in an exotic animal, bongo antelope. Several of these animals housed at the National Zoo have a thyroglobulin with an abnormal protein structure that is responsible for their goiters. Another study involves endemic goiter due to the absence of dietary iodine. Despite differences in etiology of these two goiters, i.e. abnormal thyroglobulin and iodine deficiency, both were found to secrete large amounts of albumin and cytochrome into the follicular lumen. Regulation of this abnormal secretion, and its relation to normal thyroid hormone synthesis is the direction of our present work. Also studied was thyroid tissue from a patient with congenital goiter. This patient's thyroglobulin is apparently normal in structure as well as in its acceptor function for iodination. Hypothyroidism in this patient is, however, associated with asialo-thyroglobulin. This observation is the first suggesting that sialic acid may be critical for normal processing of thyroglobulin with release of thyroid hormones.